Vascular Smooth Muscle Actions of Carnosine

Our studies into the physiological actions of carno-sine stemmed from seeking an imidazole-containing structure amongst the components of the sarcoplasm. At an early stage, we were interested to find whether any endogenous imidazoles could have properties similar to the myofilament Ca2+-sensitizing then recently first detected for caffeine. Even earlier work by one of us [1] led us to consider that the imidazole moiety in the methylxanthines such as caffeine (and its relatives such as theophylline and theobromine) was the likely key to this activity. The histidyl dipeptide carnosine ( b-alanyl-L-histi-dine), one of a group of endogenous compounds includ-ing anserine ( b-alanyl-N1-methyl-L-histidine) and homocarnosine ( g-aminobutyryl-L-histidine) seemed a candidate [2]. Carnosine occurs at high concentration in skeletal muscle (1-50 mM) [3] and figures as the most prevalent of the organic constituents of myoplasm at least in fast skeletal muscle. Its concentration is lower in cardiac muscle (~1 mM) [4] and in plasma the concen-tration is in many cases undetectable (<0.1 m M by the most sensitive method to date) [5]. Amongst the actions attributed to it (see [6]) carnosine has been implicated as: a) major organic pH buffer of skeletal muscle; b) having radical scavenging activity (see, e.g., [7]); c) an olfactory neurotransmitter and/or a neuromodulator [8]; d) influencing at least two enzymes important in the energy transduction pathway, phosphorylase a and